Nimesulide is a

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a Indication (medicine), therapeutic drug class which Analgesic, reduces pain, Anti-inflammatory, decreases inflammation, Antipyretic, decreases fever, and Antithrombotic, prevents bl ...

(NSAID) with

pain medication An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in so ...

and fever reducing properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of

osteoarthritis Osteoarthritis is a type of degenerative joint disease that results from breakdown of articular cartilage, joint cartilage and underlying bone. A form of arthritis, it is believed to be the fourth leading cause of disability in the world, affect ...

, and primary dysmenorrhoea in

adolescents Adolescence () is a transitional stage of human physical and psychological development that generally occurs during the period from puberty to adulthood (typically corresponding to the age of majority). Adolescence is usually associated with ...

and adults above 12 years old. Side effects may include

liver problems Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common. Liver diseases File:Ground gla ...

. It has a multifactorial mode of action and is characterized by a fast onset of action. It works by blocking the production of prostaglandins (a chemical associated with pain), thereby relieving pain and inflammation.

Medical uses

It may be used for pain, including period pains. Nimesulide is not recommended long-term, as for chronic conditions such as arthritis. This is due to its association with an increased risk of liver toxicity, including liver failure. Despite its risk of hepatotoxicity, a 2012 evaluation by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of pharmaceutical products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products ...

(EMA) concluded that the overall benefit/risk profile of nimesulide is favourable and in line with that of the other NSAIDs such as

diclofenac Diclofenac, sold under the brand name Voltaren among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It can be taken orally (swallowed by mouth), inserted rectally as a ...

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...

, and

naproxen Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, and inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It ...

provided that the duration of use is limited to 15 days and the dose does not exceed 200 mg/day.

Children

Less than 10 days of nimesulide does not appear to increase the risk of hypothermia, gastrointestinal bleeding, epigastric pain, vomiting, diarrhea, or transient, asymptomatic elevation of liver enzymes compared to

ketoprofen Ketoprofen is one of the propionic acid class of nonsteroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin. It was patented in 1967 and approved for medi ...

paracetamol Paracetamol, or acetaminophen, is a non-opioid analgesic and antipyretic agent used to treat fever and mild to moderate pain. It is a widely available over-the-counter drug sold under various brand names, including Tylenol and Panadol. Parac ...

mefenamic acid Mefenamic acid is a member of the Nonsteroidal anti-inflammatory drug#Anthranilic acid derivatives .28fenamates.29, anthranilic acid derivatives (or fenamate) class of nonsteroidal anti-inflammatory drugs (NSAIDs), and is used to treat mild to m ...

aspirin Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...

, or

in children. However, data does not speak to populations less than 6 months old.

Pregnancy and lactation

Women should use the drug with caution during lactation and nimesulide is contraindicated during pregnancy, and research suggest that it is also contraindicated in lactating women.

Available forms

Nimesulide is available in a variety of forms: tablets, powder for dissolution in water, suppositories, mouth dissolving tablets, and topical gel.

Contraindications

It should be avoided by children under 12 and people with liver problems.

Side effects

Due to concerns about the risk of

liver toxicity Hepatotoxicity (from ''hepatic toxicity'') implies chemical-driven liver damage. Drug-induced liver injury (DILI) is a cause of acute and chronic liver disease caused specifically by medications and the most common reason for a drug to be withdr ...

, nimesulide has been withdrawn from market in several countries (Mexico, Spain, Finland, Belgium, and Ireland). Liver problems have resulted in both deaths and the need for transplantation. The frequency of nimesulide-induced liver injury is estimated at around 1 in 50,000 patients, severe injury has occurred in as little as three days after starting the medication. Shorter (≤ 15 days) duration of therapy does not prevent serious nimesulide hepatotoxicity. Continuous use of nimesulide (more than 15 days) may cause the following side effects: * Diarrhea * Vomiting * Skin rash * Itchiness * Dizziness * Bitterness in mouth

Pharmacology

Pharmacodynamics

Nimesulide is a

(NSAID), acting specifically as a relatively selective cyclooxygenase-2 inhibitor. However, the pharmacological profile of nimesulide is peculiar, and additional, unknown/yet-to-be-identified mechanisms appear to also be involved. One pathway that has been implicated in its actions is the ecto-5'-nucleotidase (e-5′NT/CD73)/ adenosine A_2A receptor pathway.

Pharmacokinetics

Nimesulide is absorbed rapidly following oral administration. Nimesulide undergoes extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active). Food, sex, and advanced age have negligible effects on nimesulide pharmacokinetics. Moderate

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

does not necessitate dosage adjustment, while in patients with severe chronic kidney disease or liver disease, nimesulide is contraindicated. Nimesulide has a relatively rapid onset of action, with meaningful reductions in pain and inflammation observed within 15 minutes from drug intake. The therapeutic effects of nimesulide are the result of its complex mode of action, which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes, and histamine. Clinical evidence is available to support a particularly good profile in terms of gastrointestinal tolerability.

History

Nimesulide was launched in

Italy Italy, officially the Italian Republic, is a country in Southern Europe, Southern and Western Europe, Western Europe. It consists of Italian Peninsula, a peninsula that extends into the Mediterranean Sea, with the Alps on its northern land b ...

for the first time as Aulin and Mesulid in 1985 and is available in more than 50 countries worldwide, including among others

France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...

Portugal Portugal, officially the Portuguese Republic, is a country on the Iberian Peninsula in Southwestern Europe. Featuring Cabo da Roca, the westernmost point in continental Europe, Portugal borders Spain to its north and east, with which it share ...

Greece Greece, officially the Hellenic Republic, is a country in Southeast Europe. Located on the southern tip of the Balkan peninsula, it shares land borders with Albania to the northwest, North Macedonia and Bulgaria to the north, and Turkey to th ...

Switzerland Switzerland, officially the Swiss Confederation, is a landlocked country located in west-central Europe. It is bordered by Italy to the south, France to the west, Germany to the north, and Austria and Liechtenstein to the east. Switzerland ...

Belgium Belgium, officially the Kingdom of Belgium, is a country in Northwestern Europe. Situated in a coastal lowland region known as the Low Countries, it is bordered by the Netherlands to the north, Germany to the east, Luxembourg to the southeas ...

Russia Russia, or the Russian Federation, is a country spanning Eastern Europe and North Asia. It is the list of countries and dependencies by area, largest country in the world, and extends across Time in Russia, eleven time zones, sharing Borders ...

Thailand Thailand, officially the Kingdom of Thailand and historically known as Siam (the official name until 1939), is a country in Southeast Asia on the Mainland Southeast Asia, Indochinese Peninsula. With a population of almost 66 million, it spa ...

, and

Brazil Brazil, officially the Federative Republic of Brazil, is the largest country in South America. It is the world's List of countries and dependencies by area, fifth-largest country by area and the List of countries and dependencies by population ...

. Nimesulide has never been filed for

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respo ...

(FDA) evaluation in the

United States The United States of America (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...

, where it is not marketed.

Society and culture

Brand names

Nimesulide is available throughout the world as original product with the following trademarks: Sulide, Nimalox, Mesulid (Novartis, Brazil, Boehringer Ingelheim, Greece, Italy, Hungary), Coxtal (Sanofi, China, Bulgaria), Sintalgin (Abbott, Brazil), Eskaflam (GSK, Brazil, Mexico), Octaprin, Nimside (Teva, Pakistan), Nise (Russia, Venezuela, Vietnam, Ukraine), Nilsid (Egypt); Aulin (Bulgaria, Czech Republic, Italy, Romania, Poland), Ainex, Drexel, Donulide, Edrigyl, Enetra, Heugan, Mesulid, Minapon, NeRelid, Nexen, Nidolon, Nilden (Mexico); Emsulide, Nimed, Nimedex, Nimesil (Czech Republic, Moldova, Latvia, Lithuania, Kazakhstan, Georgia, Poland), Nimulid (Trinidad & Tobago), Nimutab, Nimdase, Nimopen-MP Nise, Nimuwin, Nisulid, Nodard Plus, Nicip, Nimcap, Nic-P, Nic-Spas, Nimupain (India); Mesulid, Novolid, Relmex (Ecuador); Remisid (Ukraine); Coxulid, Emulid, Frenag, Fuzo, Motival, Nimeksil, Nimelid, Nîmes, Nimesdin, Romasulid, Sulidin, Suljel, Thermo Sulidin (Turkey), Xilox (Hungary); Modact-IR (Pakistan); and ad Sulidene and Zolan for veterinary use. Many generic and copy-products also exist (Lusemin, Medicox, Nidol, Nimalox, Nimesil, Nimotas, Nimulid, Nizer, Sorini, Ventor, Vionim, Neolide, Willgo among others), new-aid, Nexulide (Syria), Nims, Nice, Nimulide (Nepal)

India

Several reports have been made of nimesulide's

adverse drug reactions An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or may result from the combination of two or more drugs. The meaning of this ...

in India. On 12 February 2011, ''

The Indian Express ''The Indian Express'' is an English-language Indian daily newspaper founded in 1932 by P. Varadarajulu Naidu. It is headquartered in Noida, owned by the ''Indian Express Group''. It was later taken over by Ramnath Goenka. In 1999, eight y ...

'' reported that the Union Ministry of Health and Family Welfare had finally decided to suspend the pediatric use of the analgesic suspension. From 10 March 2011 onward, nimesulide formulations are not indicated for human use in children below 12 years of age. On 13 September 2011, the

Madras High Court The High Court of Judicature at Madras is a High Courts of India, High Court located in Chennai, India. It has appellate jurisdiction over the state of Tamil Nadu and the union territory of Puducherry (union territory), Puducherry. It is one of ...

revoked a suspension on manufacture and sale of paediatric drugs nimesulide and

phenylpropanolamine Phenylpropanolamine (PPA), sold under many brand names, is a sympathomimetic agent used as a decongestant and appetite suppressant. It was once common in prescription and over-the-counter cough and cold preparations. The medication is taken ...

(PPA). On 30 December 2024, the

Central government A central government is the government that is a controlling power over a unitary state. Another distinct but sovereign political entity is a federal government, which may have distinct powers at various levels of government, authorized or deleg ...

banned the manufacture, sale and distribution of nimesulide and its formulations for animal use. This was in response to studies conducted at the Indian Veterinary Research Institute (IVRI) at Izatnagar, Bareilly, showing nimesulide causing lethal kidney problems in wild vultures, especially Himalayan griffon vultures, which consume the drug through carcasses of treated livestock.

EMA confirms the positive benefit/risk ratio

On September 21, 2007 the EMA released a press release on their review on the liver-related safety of nimesulide. The EMA has concluded that the benefits of these medicines outweigh their risks, but that there is a need to limit the duration of use to ensure that the risk of patients developing liver problems is kept to a minimum. Therefore, the EMA has limited the use of systemic formulations (tablets, solutions, suppositories) of nimesulide to 15 days.

Irish Medicines Board

The Irish Medicines Board has decided to suspend Nimesulide from the Irish market and refer it to the EU Committee for Human Medicinal Products (CHMP) for a review of its benefit/risk profile. The decision is due to the reporting of six cases of potentially-related liver failures to the IMB by the National Liver Transplant Unit, St. Vincent's University Hospital. These cases occurred in the period from 1999 to 2006.

Bribes

In May 2008, Italy's leading daily paper ''

Corriere della Sera (; ) is an Italian daily newspaper published in Milan with an average circulation of 246,278 copies in May 2023. First published on 5 March 1876, is one of Italy's oldest newspapers and is Italy's most read newspaper. Its masthead has remain ...

'' and other media outlets reported that a top-ranking official at Italy's medicines agency AIFA had been filmed by police while accepting bribes from employees of pharmaceutical companies. The money allegedly was being paid to ensure that certain drugs would be spared scrutiny from the drugs watchdog. The investigation had started in 2005 following suspicions that some AIFA drug tests had been faked. Eight arrests were made. Nimesulide can be bought carrying a prescription from a physician that is kept as a receipt at the chemist shop, nominally allowing strong control over selling. The original manufacturer of nimesulide is Helsinn Healthcare SA, Switzerland, which acquired the rights for the drug in 1976. After the patent protection terminated in 2015, a number of other companies started production and marketing of Nimesulide.

References

{{Prostanoid signaling modulators Antipyretics Drugs with unknown mechanisms of action Hepatotoxins Nitrobenzene derivatives Nonsteroidal anti-inflammatory drugs Phenol ethers Withdrawn drugs